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人类挑战模型中流感防护的免疫相关因素。

Immune correlates of protection against influenza in the human challenge model.

作者信息

Treanor J, Wright P F

机构信息

Infectious Diseases Unit, University of Rochester Medical Center, Rochester, NY 14642, USA.

出版信息

Dev Biol (Basel). 2003;115:97-104.

PMID:15088780
Abstract

Intranasal administration of laboratory passaged wild-type influenza viruses to adults induces a mild upper respiratory illness accompanied by nasopharyngeal shedding of virus. A second model has used inoculation of children with attenuated viruses as a surrogate for wild-type infection. Generally, results of studies of antiviral or vaccine approaches in the challenge model have been predictive of efficacy in the real world, but it is recognized that the model does not reproduce naturally acquired illness well and both viral shedding and symptoms in the challenge model are mostly restricted to the upper respiratory tract. Serum antibody plays a major role in protection in this model and it is difficult to infect adults who have serum HI titres of > 1:8. Among adults with lower levels of HI antibody, a variety of protective factors have been described, including nasal IgA and serum NI antibody, and CTL. In some challenge studies, subjects have been protected despite lack of a measurable immune response to vaccination. Because measurement of mucosal antibody has been difficult to standardize, there is not a level that can be considered a cut-off for susceptibility. Use of a consistent method for assessing mucosal IgA between studies may help to derive a target level for vaccination.

摘要

给成年人经鼻接种实验室传代的野生型流感病毒会引发轻度上呼吸道疾病,并伴有鼻咽部病毒脱落。另一种模型是用减毒病毒接种儿童作为野生型感染的替代。一般来说,在攻毒模型中进行的抗病毒或疫苗方法研究结果已被证明能预测在现实世界中的疗效,但人们认识到该模型不能很好地重现自然获得性疾病,且攻毒模型中的病毒脱落和症状大多局限于上呼吸道。血清抗体在该模型的保护中起主要作用,血清血凝抑制(HI)效价>1:8的成年人很难被感染。在HI抗体水平较低的成年人中,已描述了多种保护因素,包括鼻腔IgA、血清中和(NI)抗体和细胞毒性T淋巴细胞(CTL)。在一些攻毒研究中,尽管对疫苗接种没有可测量的免疫反应,但受试者仍受到了保护。由于黏膜抗体的测量难以标准化,所以不存在一个可被视为易感性临界值的水平。在研究之间使用一致的方法评估黏膜IgA可能有助于得出疫苗接种的目标水平。

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